细菌生物膜的相关性研究

随着感染性疾病的不断增多和反复发作,关于细菌耐药性的研究已经成为人类关注和研究的重点。细菌生物膜在细菌耐药过程中发挥了重要的作用,且生物膜的耐药现象呈不断增高趋势,使得我们不断地研究生物膜的耐药机制及其防治措施,改进与生物膜相关疾病的治疗方法。本文将对细菌生物膜的形成、耐药机制及生物膜相关疾病的治疗现状做一综述。     

铜绿假单胞菌生物膜耐药的研究进展

铜绿假单胞菌(PA)是医院内感染最常见的细菌之一,是重症监护室内肺部感染的重要条件致病菌,且极易产生获得性耐药,可通过β内酰胺酶及氨基苷类钝化酶等灭活酶的产生、抗生素作用靶位改变、降低膜通透性、主动外排系统排出及形成生物膜等方式对多种抗生素耐药,增加临床治疗的难度.其中生物膜的形成为细菌耐药的重要机制之一,是许多感染性疾病反复发作和难以控制的主要原因.生物膜形成后特殊基因的表达也是生物膜对抗菌药物耐药的一个原因.本文重点论述PA生物膜耐药方面的研究进展.     

细菌生物膜与慢性鼻-鼻窦炎的临床研究

目的探讨细菌生物膜(BF)与慢性鼻-鼻窦炎的临床关系,分析细菌生物膜与难治性鼻窦炎的相关性。方法选择研究组24例慢性鼻-鼻窦炎(CRS)或伴有鼻息肉和对照组22例无CRS的鼻中隔偏曲患者,在扫描电镜及透视电镜下检测细菌生物膜是否存在,并对细菌生物膜的存在与部分临床指标进行相关分析。结果研究组24例患者中发现14例有细菌生物膜形成,对照组22例患者中发现2例有细菌生物膜形成,2组比较差异有统计学意义(P<0.01)。细菌生物膜阳性与细菌生物膜阴性的慢性鼻-鼻窦患者的症状VAS评分、鼻窦CT评分比较差异亦有统计学意义(P<0.05)。结论细菌生物膜在CRS患者中普遍存在,细菌生物膜与CRS的发病及其严重程度相关,是导致难治性鼻窦炎重要因素之一。     

细菌生物膜及其相关感染性疾病的研究进展

自从抗生素问世之后，细菌感染在相当长的一段时间内受到了控制。尤其是急性细菌感染，抗生素治疗往往能收到良好的疗效。但近20年来人们发现，抗生素用量不断加大而疗效却难以令人满意；抗生素不得不更新换代，然而耐药菌株则不断涌现。这其中的原因固然与滥用抗生素使得细菌变异加快有关，但也与细菌生物膜类感染密切相关。从目前所掌握的临床研究材料来看，长期慢性细菌感染、抗生素耐药现象和医院内感染都与细菌生物膜类感染相关，据估计大约65％人类细菌性感染是由细菌生物膜细菌引起的。同时细菌生物膜细菌对抗生素和宿主免疫防御机制的抗性很强，感染部位的细菌一旦形成生物膜或生物材料污染的细菌形成了生物膜，即使使用正常剂量成百倍的药物也不易治愈，成为临床上难治性感染的重要原因之一，从而导致严重的临床问题，尤其是慢性和难治的感染性疾病，因此引起了人们的极大关注。     

医学植入物相关感染诊断、预防和治疗新技术

医学植入物的应用随着医学的发展而发展,植入物相关感染的发生也在院内获得性感染中占据重要地位。细菌黏附在植入物表面形成生物膜,生物膜下的细菌即为生物膜细菌。生物膜细菌有着独特的生物学特性,具有极强的抗生素抵抗性,是医学植入物感染最重要的致病机制。预防生物膜的形成、加速生物膜的降解、杀灭生物膜细菌是预防和治疗植入物感染的研究重点。     

Correlation between bacterial biofilm and chronic rhinosinusitis

目的 探讨细菌生物膜(BF)与慢性鼻-鼻窦炎的临床关系,分析细菌生物膜与难治性鼻窦炎的相关性.方法 选择研究组24例慢性鼻-鼻窦炎(CRS)或伴有鼻息肉和对照组22例无CRS的鼻中隔偏曲患者,在扫描电镜及透视电镜下检测细菌生物膜是否存在,并对细菌生物膜的存在与部分临床指标进行相关分析.结果 研究组24例患者中发现14例有细菌生物膜形成,对照组22例患者中发现2例有细菌生物膜形成,2组比较差异有统计学意义(P＜0.01).细菌生物膜阳性与细菌生物膜阴性的慢性鼻-鼻窦患者的症状VAS评分、鼻窦CT评分比较差异亦有统计学意义(P＜0.05).结论 细菌生物膜在CRS患者中普遍存在,细菌生物膜与CRS的发病及其严重程度相关,是导致难治性鼻窦炎重要因素之一.     

肺炎克雷伯菌生物膜形成及调控机制的研究进展

生物膜是细菌生长的动态过程,其产生的胞外成分可增强细菌对宿主防御机制和抗生素的抵抗力。耐药细菌生物膜的形成将是临床感染治疗与控制的一大挑战。肺炎克雷伯菌是临床常见的致病菌,高毒力型肺炎克雷伯菌与耐碳青霉烯肺炎克雷伯菌可引起严重的感染性疾病,难以治愈,其生物膜的形成使这种情况更加严峻。对肺炎克雷伯菌生物膜形成及其调控机制的深入研究可为临床抗感染治疗与控制带来新的思路。本文主要从菌毛、多糖、群体感应系统和外排泵对肺炎克雷伯菌生物膜形成的作用及调控机制的最新研究进展进行综述。     

两药联合对铜绿假单胞菌生物膜作用研究进展

铜绿假单胞菌（PA）已成为院内感染的一个重要致病菌,其诱发疾病的特点呈慢性并反复急性发作,死亡率高。铜绿假单胞茵生物被膜（BF）的形成是其重要原因之一。细菌的生物膜能保护细菌抵御抗生素的作用形成耐药性,并能逃避机体免疫系统的攻击,从而造成慢性难治性感染。查阅近年有关文献表明,单种药物很难清除细菌生物被膜,药物联合在防治细菌生物膜感染方面具有独特的优势。该文就抗生素联合、中药联合抗生素抗铜绿假单胞菌生物膜的研究进行综述。     

慢性伤口细菌生物膜的临床识别和影响因素的研究进展

现代研究发现细菌生物膜与慢性伤口感染和难以愈合有关,如何防治细菌生物膜及其相关危害已成为目前研究的前沿和热点,文中就慢性伤口细菌生物膜的临床识别技术、诊断标准、细菌识别结果及生物膜形成的影响因素作一综述。     

细菌生物膜感染的研究进展

生物膜是附着在有生命或无生命物体表面的由细菌自身产生的多聚基质包裹的菌细胞结构群体,医学上估计超过80%人类感染性疾病是由生物膜介导。文中就当前细菌生物膜研究发展的特点、生物膜形成机制和影响因素的一些的认识以及在细菌生物膜防治方面取得的进展作一综述。     

Bacterial biofilm and associated infections

Microscopic entities, microorganisms that drastically affect human health need to be thoroughly investigated. A biofilm is an architectural colony of microorganisms, within a matrix of extracellular polymeric substance that they produce. Biofilm contains microbial cells adherent to one-another and to a static surface (living or non-living). Bacterial biofilms are usually pathogenic in nature and can cause nosocomial infections. The National Institutes of Health (NIH) revealed that among all microbial and chronic infections, 65% and 80%, respectively, are associated with biofilm formation. The process of biofilm formation consists of many steps, starting with attachment to a living or non-living surface that will lead to formation of micro-colony, giving rise to three-dimensional structures and ending up, after maturation, with detachment. During formation of biofilm several species of bacteria communicate with one another, employing quorum sensing. In general, bacterial biofilms show resistance against human immune system, as well as against antibiotics. Health related concerns speak loud due to the biofilm potential to cause diseases, utilizing both device-related and non-device-related infections. In summary, the understanding of bacterial biofilm is important to manage and/or to eradicate biofilm-related diseases. The current review is, therefore, an effort to encompass the current concepts in biofilm formation and its implications in human health and disease.     

Activity of ciprofloxacin and azithromycin on biofilms produced in vitro by Haemophilus influenzae

Background It is recognized that Haemophilus influenzae isolated from patients with otitis media forms biofilms both in vitro and in vivo, suggesting that biofilm formation in vivo might play an important role in the pathogenesis and chronicity of otitis media, but the effect of antibiotics on biofilm has not been well studied. We investigated the impact of ciprofloxacin and azithromycin on bacterial biofilms formed by Haemophilus influenzae in vitro in this study. Methods Eleven strains of Haemophilus influenzae were isolated from sputum specimens collected from patients with acute exacerbation of chronic obstructive pulmonary diseases. Formation of bacterial biofUm was examined by crystal violet assay and a scanning electron microscope. Alterations of biofilms were measured under varying concentrations of azithromycin and ciprofloxacin. Results Striking differences were observed among strains with regard to the ability to form biofilm. Typical membrane-like structure formed by bacterial cells and extracellular matrix was detected. Initial biofilm synthesis was inhibited by azithromycin and ciprofloxacin at concentrations higher than two-fold minimal inhibitory concentration. Disruption of mature biofilms could be achieved at relatively higher concentration, and ciprofloxacin displayed more powerful activity. Conclusions Haemophilus influenzae is capable of forming biofilm in vitro. Sufficient dosage might control early formation of biofilms. Ciprofloxacin exerts better effects on breakdown of biofilm than azithromycin at conventional concentration in clinics.     

Morphology of bacterial flora in root canals associated with apical abscesses

Background Apical abscess is an inflammatory process in the peri-radicular tissues caused by biofilms in the necrotic root canal systems. Therefore, a comprehensive analysis of the bacterial colonization is required for a better understanding of the pathogenesis. This study aimed to investigate the patterns of bacterial infection of root canals of teeth with apical abscesses and to determine whether histological and microbiological findings correlated with clinical conditions. Methods Eighteen samples from 18 teeth with apical pathological lesions were analyzed. Nine patients with acute apical abscesses experienced severe pain, and nine patients were asymptomatic with a sinus tract. After extraction, each affected root was divided into two halves. One half was processed for histobacteriologic analysis and examined using light microscopy, and the other half was analyzed using scanning electron microscopy （SEM） to determine the patterns of microbial colonization of the root canals. Results The appearance of each sample subjected to SEM was consistent with the histobacteriologic findings despite the presence or absence of clinical symptoms. Intraradicular biofilms comprising cocci, rods, and/or filaments of amorphous materials were observed in the apical third of the main root canals in all samples. The bacterial biofilms covering the main root canal walls also penetrated the dentinal tubules to varying depths. The morphologies of biofilms varied, and a unique pattern of intraradicular infection was not identified. Conclusion Intraradicular infections formed complex and variable multispecies biofilms and their presence did not correlate with clinical symptoms.     

细菌鞭毛的运动性在生物膜形成中的双重作用

生物膜是细菌感染的重要方式,生物膜所致的高度耐药性已经越来越威胁到人类健康。鞭毛在生物膜形成中的重要性已经被医学界广泛接受,普遍认为鞭毛的运动性与生物膜的形成能力成正比。然而,近年来多项研究表明,并非所有细菌的鞭毛都促进生物膜的形成,在环二核苷酸等分子作用下抑制细菌鞭毛的合成和运动性后,细菌生物膜的合成和稳定性显著增强。     

The action of Pseudomonas aeruginosa biofilms in intrinsic drug resistance

Background There is a growing interest in studying the relationship between intrinsic resistance and biofilms resistance to drugs. However, the relationship still remains unclear in the macroscopic bacterial growth. Our study is to illuminate the change of bacterial drug resistance of gyrA mutant and active efflux pump during the development of Pseudomonas aeruginosa （ P. aeruginosa ） biofilms. Methods The strains of typeⅡ topoisomerase gene mutant （gyrA mutant） and multidrug resistance （MDR） efflux pump were clinical isolates and detected by polymerase chain reaction （PCR）. The process of bacterial biofilms development was observed by scanning electron microscope. Triparental mating experiments were performed to transfer report gene of green fluorescent protein （GFP） into P. aeruginosa biofilms strains and followed by analysis of bacterial survival rate between intrinsic resistance and biofilms resistance. Results The fluorescent strains with pGFPuv could develop mature biofilms on Teflon surface. Before a period of 72 hours, the survival rate of biofilms bacteria and intrinsic resistance strains in ciprofloxacin solution was significantly different （ P 〈 0.05）. The survival number of intrinsic resistance strains （gyrA mutation and active efflux pump） was illustriously higher than biofilm strain in the initial stage of biofilms development. After 72 hours incubation, there was no clearly difference between mutants and biofilms strains in the survival rate （P 〉 0.05）. The carbonyl cyanide m-chlorophenylhydrazone and azithromycin could significantly reduce the drug resistance of biofilm strains and efflux pump strains. Conclusions In the development of P. aeruginosa biofilms, the strains of gyrA mutation and MDR efflux could be conferred with new level of drug resistance. When co-cultured mutated strains with biofilm strains, biofilms may play a major role in bacterial resistance. But after 72 hours incubation （ a mature biofilms had been developed） , there was no clearly difference between the number of mutant strains and biofilm strains.     

骨折内固定术后感染的诊断和治疗

骨折内固定术后感染的发病机制与黏附其上的微生物有关,大多由开放性骨折和骨折内固定手术中的葡萄球菌引起。按感染的时间分为早期(<2周)、延期(2～10周)和晚期感染(>10周),早期准确诊断骨折内固定术后感染较困难。PET和PET-CT技术的出现为诊断骨折内固定术后感染提供了一种新工具。治疗感染的目的是巩固骨质并预防慢性骨髓炎的发生,要求用合适的外科手术联合6～12周抗生素来彻底治愈感染。本文综述了髓内钉、外固定支架、钢板和螺钉相关性感染的发病机制、分类、诊断及其治疗方法。     

附属基因调节子在葡萄球菌生物被膜形成与感染中的作用

葡萄球菌生物被膜是生物材料相关感染病理学中最重要的毒力因子,生物被膜形成是由群集感应系统调节的。葡萄球菌附属基因调节子agr作为群集感应系统具有种属特异性,在金黄色葡萄球菌和表皮葡萄球菌中控制着一系列毒素和毒力因子的表达,而且与天然免疫系统互作。新的研究进展表明附属基因调节子agr在体内感染中的作用非常微妙。这方面的进展有助于发掘新型抗菌剂和消除与装置相关的葡萄球菌生物被膜感染问题。     

Clinical and histopathologic features of biofilm-associated chronic rhinosinusitis with nasal polyps in Chinese patients

Background  Biofilms have given new insights to the understanding of pathogenesis of chronic rhinosinusitis (CRS). However, the link between biofilms formation and local inflammatory response remains poorly defined in CRS with nasal polys. The aim of this study was to determine the potential association of the presence of biofilms in the nasal mucosal tissues with clinical features in Chinese patients, which had CRS with nasal polyps (CRSwNP).

Methods  A total of 19 patients with CRSwNP and 12 patients with non-CRS were subjected to endoscopic surgery and their nasal mucosal tissue specimens were examined histologically and by scanning electron microscopy (SEM). Their demographic and clinical features were recorded.

Results  Thirteen (68.4%) out of the 19 specimens from patients with CRSwNP, but none from control patients, were positive for biofilms that displayed typical characteristics of bacterial and fugal structures. The presence of biofilms in the nasal mucosal tissues was associated with significantly greater values of purulent nasal discharge and preoperative Lund-Kennedy scores, higher levels of serum total IgE and percentages of subjects with endoscopic surgery (ESS) history in patients with CRSwNP, and more severe inflammation in the nasal mucosal tissues of patients with CRSwNP.

Conclusion  Our study demonstrated the presence of biofilms in the nasal mucosal tissues of many patients, contributing to the understanding of the pathogenic process of CRSwNP in Chinese patients.

     

14、15环-大环内酯类药物在清除铜绿假单胞菌生物膜中的作用

目的研究14、15环-大环内酯类药物及抗铜绿假单胞菌药物对铜绿假单胞菌生物膜的清除作用.方法以硅胶片制备生物膜后,与不同抗生素相互作用一定的时间后,进行硅胶片菌落计数,观察药物对细菌生物膜的清除作用.结果MH空白对照组各时间段的BF内细菌存活率没有显著差异,单加MPM、AMK和MPM、AMK与MDM联合用药处理组的BF内细菌存活率与空白对照组相近.MPM、AMK与AZ或EM组合用药处理组的BF内细菌存活率在各时间段明显下降.结论红霉素、阿奇霉素可增强抗铜绿假单胞菌药物对生物膜的渗透性,对抗铜绿假单胞菌药物杀灭生物膜内细菌有增效作用.     

Evaluation of an anti-infective combination. Trimethoprim-sulfamethoxazole (Bactrim, Septra).

Trimethoprim and sulfamethoxazole, combined in a synthetic anti-infective preparation, act synergistically to inhibit the growth of certain microorganisms. This combination is effective orally in acute and chronic urinary tract infections. It also has been used successfully to treat other infectious conditions, including bacterial upper respiratory tract infections, ear infections, skin and soft-tissue infections, septicemias, acute and subacute bacterial endocarditis, enteric fever, brucellosis, prostatitis, and gonorrhea. It is well tolerated by most patients.